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A series of chalcones (1–9) and pyrazoles (10–18) was prepared to investigate their potential activity as Angiotensin I-Converting Enzyme (ACE) inhibitors. Their structures were verified by elemental analysis, UV, IR, MS, 1H NMR, 13C NMR, and 2D NMR experiments. Among tested compounds, chalcone 7 exerted the highest activity with an IC50 value of 0.219 mM, while the most potent pyrazole was 15 (IC50 value of 0.213 mM).  相似文献   
884.
MK-0674 is a potent and selective cathepsin K inhibitor from the same structural class as odanacatib with a comparable inhibitory potency profile against Cat K. It is orally bioavailable and exhibits long half-life in pre-clinical species. In vivo studies using deuterated MK-0674 show stereoselective epimerization of the alcohol stereocenter via an oxidation/reduction cycle. From in vitro incubations, two metabolites could be identified: the hydroxyleucine and the glucuronide conjugate which were confirmed using authentic synthetic standards.  相似文献   
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Previously described SAR of benzimidazole-based non-nucleoside finger loop (Thumb Pocket I) inhibitors of HCV NS5B polymerase was expanded. Prospecting studies using parallel synthesis techniques allowed the rapid identification of novel cinnamic acid right-hand sides that provide renewed opportunities for further optimization of these inhibitors. Novel diamide derivatives such as 44 exhibited comparable potency (enzymatic and cell-based HCV replicon) as previously described tryptophan-based inhibitors but physicochemical properties (e.g., aqueous solubility and lipophilicity) have been improved, resulting in molecules with reduced off-target liabilities (CYP inhibition) and increased metabolic stability.  相似文献   
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  • 1 Rising economic demands for boreal forest resources along with current and predicted increases in wildfire activity have increased salvage logging of burned forests. Currently, the ecological consequences of post‐fire salvage logging are insufficiently understood to develop effective management guidelines or to adequately inform policy decision‐makers.
  • 2 We used both field and laboratory studies to examine the effects of post‐fire salvage logging on populations of the white‐spotted sawyer Monochamus scutellatus scutellatus (Say) (Coleoptera: Cerambycidae) and its ecological function in boreal forest.
  • 3 Monochamus s. scutellatus adults were relatively abundant in both burned and clear‐cut logged sites but were absent from salvage logged sites.
  • 4 An in situ mesocosm experiment showed that the abundance of M. s. scutellatus larvae in burned white spruce bolts was linked to changes in total organic nitrogen and carbon in mineral soil.
  • 5 Organic nutrient inputs in the form of M. s. scutellatus frass increased mineral soil microbial respiration rates by more than three‐fold and altered the availability of nitrogen. Changes in nitrogen availability corresponded with decreased germination and growth of Epilobium angustifolium and Populus spp. but not Calamagrostis canadensis.
  • 6 Although the present study focused on local scale effects, the reported findings suggest that continued economic emphasis on post‐fire salvage logging may have implications beyond the local scale for biodiversity conservation, nutrient cycling and plant community composition in forest ecosystems recovering from wildfire.
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Background  

Follicular fluid contains substances involved in follicle activity, cell differentiation and oocyte maturation. Studies of its components may contribute to better understanding of the mechanisms underlying follicular development and oocyte quality. The canine species is characterized by several ovarian activity features that are not extensively described such as preovulatory luteinization, oocyte ovulated at the GV stage (prophase 1) and poly-oocytic follicles. In this study, we examined the hypothesis that the preovulatory LH surge is associated with changes in steroid and protein content of canine follicular fluid prior to ovulation.  相似文献   
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